1. Field of the Invention
This invention relates to microspheres capable of releasing a drug after a predetermined period of time. More particularly, it relates to microspheres which are adapted for intracerebral implantation having the purpose of suppressing cerebral vasospasm.
2. Description of the Prior Art
As microcapsules or microspheres used for the purpose of releasing a drug gradually over a long period of time, a great variety of pharmaceutical preparations made by supporting drugs on various carriers and polymeric matrices have been proposed.
Typical processes for the production of such pharmaceutical preparations include, for example, a process involving the formation of a W/O/W emulsion as described in Japanese Patent Laid-Open No. 201816/'87. Moreover, processes developed with a view to overcoming the disadvantages of such production process (e.g., a low degree of drug incorporation into the polymeric matrix, and a premature burst of the drug from microspheres) have also be proposed (see Japanese Patent Laid-Open Nos. 145046/'94 and 32732/'94).
However, these pharmaceutical preparations have the common purpose of releasing the drug steadily from the carrier over a long period of time, and successful examples of such release have been disclosed.
On the other hand, prolonged drug-releasing type pharmaceutical preparations which are to be implanted in particular organs for the purpose of treating special diseases have also be proposed. As a specific example of such pharmaceutical preparations, Japanese Patent Application No. 50953/'94 discloses a pharmaceutical preparation which uses a complex of a water-soluble polymer, an oil, a fatty acid and the like as the carrier and serves to suppress cerebral vasospasm, and also suggests that the timing of drug release can be controlled.
In order to effectively prevent or treat certain diseases as described above, including cerebral vasospasm accompanying abnormal contractions of cerebral blood vessels observed after a definite period of time has elapsed after the rupture of a cerebral aneurysm, it is important to release the drug with controlled timing instead of releasing it simply in a steady manner. For example, the above-described cerebral vasospasm comprehends early spasm observed within 24 hours after the rupture of a cerebral aneurysm and delayed spasm observed 4 days to 2 weeks after that, and the latter is considered to be of particular interest from a clinical point of view.
Under these circumstances, it would be meaningful to provide a pharmaceutical preparation in which the timing of drug release can be controlled as described in Japanese Patent Application No. 50953/'94, i.e., a major portion of the drug can be concentratively released after the lapse of a predetermined period of time (which preparation will be referred to herein as a "delayed drug-releasing type" pharmaceutical preparation).
Although delayed drug-releasing type pharmaceutical preparations have already been provided as described above, it is still desired to provide a further improved pharmaceutical preparation or drug delivery system having such a mode of drug release. Accordingly, an object of the present invention is to provide a drug delivery system of the delayed releasing type which can release the drug concentratively after the lapse of a predetermined period of time, instead of releasing it steadily.